High product purity is an important criterion for the manufacture of a safe and effective pharmaceutical. HMG-CoA reductase inhibitors, such as lovastatin, simvastatin and pravastatin, are a recently introduced new class of cholesterol-lowering agents that effectively lower plasma cholesterol but must be taken on a long term basis. Thus it is particularly critical that HMG-CoA reductase inhibitors be administered in the highest possible purity.
The present purification procedure for HMG-CoA reductase inhibitors involves a solid absorption operation and at least two recrystallizations. This procedure yields a product purity of .about.99.0%. It would be highly desirable to employ a purification process that would yield a product purity greater than 99.5% and use no more than one recrystallization with a recyclable solvent and be adaptable to a high production volume.
High performance liquid chromatography (HPLC) is commonly used for the analytical determinations of compound purity. HPLC for large scale industrial solution preparations (preparative HPLC) has been employed in the separation and and purification of proteins but it is believed not to have been employed in the large scale purification of relatively small molecules such as HMG-CoA reductase inhibitors.